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Regulation of p53Function andStability byPhosphorylation Margaret AshcroftMichael H.G. KubbutatKaren H. Vousden1999 год

Regulation of p53 Function and Stability by Phosphorylation
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Аннотация: The p53 tumor suppressor protein can be phosphorylated at several sites within the N- and C-terminal domains, and several protein kinases have been shown to phosphorylate p53 in vitro. In this study, we examined the activity of p53 proteins with combined mutations at all of the reported N-terminal phosphorylation sites (p53N-term), all of the C-terminal phosphorylation sites (p53C-term), or all of the phosphorylation sites together (p53N/C-term). Each of these mutant proteins retained transcriptional transactivation functions, indicating that phosphorylation is not essential for this activity of p53, although a subtle contribution of the C-terminal phosphorylation sites to the activation of expression of the endogenous p21(Waf1/Cip1)-encoding gene was detected. Mutation of the phosphorylation sites to alanine did not affect the sensitivity of p53 to binding to or degradation by Mdm2, although alteration of residues 15 and 37 to aspartic acid, which could mimic phosphorylation, resulted in a slight resistance to Mdm2-mediated degradation, consistent with recent reports that phosphorylation at these sites inhibits the p53-Mdm2 interaction. However, expression of the phosphorylation site mutant proteins in both wild-type p53-expressing and p53-null lines showed that all of the mutant proteins retained the ability to be stabilized following DNA damage. This indicates that phosphorylation is not essential for DNA damage-induced stabilization of p53, although phosphorylation could clearly contribute to p53 stabilization under some conditions.
Год издания: 1999
Авторы: Margaret Ashcroft, Michael H.G. Kubbutat, Karen H. Vousden
Издательство: Taylor & Francis
Источник: Molecular and Cellular Biology
Ключевые слова: Cancer-related Molecular Pathways, Ubiquitin and proteasome pathways, Epigenetics and DNA Methylation
Другие ссылки: Molecular and Cellular Biology (HTML)
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Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
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